Amalaki rasayana, a traditional Indian drug enhances cardiac mitochondrial and contractile functions and improves cardiac function in rats with hypertrophy.

We evaluated the cardioprotective effect of Amalaki Rasayana (AR), a rejuvenating Ayurvedic drug prepared from Phyllanthus emblica fruits in the reversal of remodeling changes in pressure overload left ventricular cardiac hypertrophy (LVH) and age-associated cardiac dysfunction in male Wistar rats. Six groups (aging groups) of 3 months old animals were given either AR or ghee and honey (GH) orally; seventh group was untreated. Ascending aorta was constricted using titanium clips in 3 months old rats (N = 24; AC groups) and after 6 months, AR or GH was given for further 12 months to two groups; one group was untreated. Histology, gene and protein expression analysis were done in heart tissues. Chemical composition of AR was analyzed by HPLC, HPTLC and LC-MS. AR intake improved (P < 0.05) cardiac function in aging rats and decreased LVH (P < 0.05) in AC rats as well as increased (P < 0.05) fatigue time in treadmill exercise in both groups. In heart tissues of AR administered rats of both the groups, SERCA2, CaM, Myh11, antioxidant, autophagy, oxidative phosphorylation and TCA cycle proteins were up regulated. ADRB1/2 and pCREB expression were increased; pAMPK, NF-kB were decreased. AR has thus a beneficial effect on myocardial energetics, muscle contractile function and exercise tolerance capacity.

A novel gene THSD7A is associated with obesity.

Body mass index (BMI) is a non-invasive measurement of obesity. It is commonly used for assessing adiposity and obesity-related risk prediction. Genetic differences between ethnic groups are important factors, which contribute to the variation in phenotypic effects. India inhabited by the first out-of-Africa human population and the contemporary Indian populations are admixture of two ancestral populations; ancestral north Indians (ANI) and ancestral south Indians (ASI). Although ANI are related to Europeans, ASI are not related to any group outside Indian-subcontinent. Hence, we expect novel genetic loci associated with BMI. In association analysis, we found eight genic SNPs in extreme of distribution (P⩽3.75 × 10(-5)), of which WWOX has already been reported to be associated with obesity-related traits hence excluded from further study. Interestingly, we observed rs1526538, an intronic SNP of THSD7A; a novel gene significantly associated with obesity (P=2.88 × 10(-5), 8.922 × 10(-6) and 2.504 × 10(-9) in discovery, replication and combined stages, respectively). THSD7A is neural N-glycoprotein, which promotes angiogenesis and it is well known that angiogenesis modulates obesity, adipose metabolism and insulin sensitivity, hence our result find a correlation. This information can be used for drug target, early diagnosis of obesity and treatment.

In vivo effects of traditional Ayurvedic formulations in Drosophila melanogaster model relate with therapeutic applications.

BACKGROUND: Ayurveda represents the traditional medicine system of India. Since mechanistic details of therapy in terms of current biology are not available in Ayurvedic literature, modern scientific studies are necessary to understand its major concepts and procedures. It is necessary to examine effects of the whole Ayurvedic formulations rather than their "active" components as is done in most current studies. METHODS: We tested two different categories of formulations, a Rasayana (Amalaki Rasayana or AR, an herbal derivative) and a Bhasma (Rasa-Sindoor or RS, an organo-metallic derivative of mercury), for effects on longevity, development, fecundity, stress-tolerance, and heterogeneous nuclear ribonucleoprotein (hnRNP) levels of Drosophila melanogaster using at least 200 larvae or flies for each assay. RESULTS: A 0.5% (weight/volume) supplement of AR or RS affected life-history and other physiological traits in distinct ways. While the size of salivary glands, hnRNP levels in larval tissues, and thermotolerance of larvae/adult flies improved significantly following feeding either of the two formulations, the median life span and starvation resistance improved only with AR. Feeding on AR or RS supplemented food improved fecundity differently. Feeding of larvae and adults with AR increased the fecundity while the same with RS had opposite effect. On the contrary, feeding larvae on normal food and adults on AR supplement had no effect on fecundity but a comparable regime of feeding on RS-supplemented food improved fecundity. RS feeding did not cause heavy metal toxicity. CONCLUSIONS: The present study with two Ayurvedic formulations reveals formulation-specific effects on several parameters of the fly's life, which seem to generally agree with their recommended human usages in Ayurvedic practices. Thus, Drosophila, with its very rich genetic tools and well-worked-out developmental pathways promises to be a very good model for examining the cellular and molecular bases of the effects of different Ayurvedic formulations.

Chitra heart valve: results of a multicenter clinical study.

BACKGROUND AND AIM OF THE STUDY: The Chitra tilting disc valve was developed in India to meet the need for a low-cost cardiac valve. The valve has an integrally machined cobalt-based alloy cage, an ultra-high molecular-weight polyethylene disc, and a polyester suture ring. An important feature of this valve is its soft closing sound, by virtue of a plastic occluder. METHODS: Between December 1990 and January 1995, 306 patients underwent isolated aortic (AVR, n = 101) or mitral valve replacement (MVR, n = 205) at six institutions in India. The early mortality rate was 6.9% (seven after AVR; 14 after MVR). A total of 285 survivors was followed up until September 1998; total follow up was 1212 patient-years (pt-yr) (AVR, 445 pt-yr; MVR, 767 pt-yr). RESULTS: There were 52 late deaths (4.3%/pt-yr; AVR 2.2%/pt-yr; MVR 5.5%/pt-yr). Thirty-five deaths were valve-related (23 were due to unknown causes). One AVR patient (0.2%/pt-yr) and 12 MVR patients (1.6%/pt-yr) developed valve thrombosis, and embolic episodes occurred in 25 patients (seven after AVR, 1.6%/pt-yr; 18 after MVR, 2.4%/pt-yr). Bleeding events and infectious endocarditis occurred infrequently (AVR 0.9 and 0.7%/pt-yr; MVR 0.4 and 0.5%/pt-yr, respectively). There was no incidence of paravalvular leak or structural dysfunction of the valve. Actuarial survival rates at seven years were 82.4+/-4.0% for AVR and 65.2+/-5.0% for MVR. During the same interval, thrombus-free and embolism-free survival after AVR and MVR occurred in 98.9+/-1.1% and 94.1+/-1.9%, and 92.3+/-2.8% and 82.1+/-5.7% of patients, respectively. Freedom from all valve-related mortality and morbidity at seven years was 81.5+/-4.1% after AVR, and 64.2+/-5.1% after MVR. CONCLUSION: The Chitra valve appears to be safe and to have performance comparable with that of other currently used tilting disc valves. This valve costs substantially less than other valves, and is therefore within reach of a larger subset of Indian patients.

Cerium levels are elevated in the serum of patients with endomyocardial fibrosis (EMF).

The geochemical hypothesis on endomyocardial fibrosis (EMF) links causation of the disease to increased levels of cerium in the heart. Since cardiac tissues are not easily accessible from patients, we explored whether cerium can be detected in the serum using neutron activation analysis (NAA). Cerium levels in serum of EMF patients were significantly elevated (p < 0.05) compared to controls.

Development of the Chitra tilting disc heart valve prosthesis.

BACKGROUND AND AIMS OF THE STUDY: The high prevalence of rheumatic valvular disease in the young population and the high cost of imports necessitated the development of an Indian valve. The development of a tilting disc prosthesis was successfully concluded in February 1995, when the third model completed its clinical trial. The tilting disc valve has an integrally machined cobalt alloy cage, an ultra high molecular weight polyethylene disc and a polyester suture ring. The choice of design was based on its superior hydrodynamics and the age distribution of patients, the majority of whom were below 30 years. The polymer-metal combination was selected for its extremely low wear rate and proven durability in the human body. MATERIALS AND METHODS: The hydrodynamic performance was tested under steady and pulsatile flow conditions. The accelerated durability of nine test valves was evaluated at 800-840 cycles/min for over 350 million cycles each. Size 23 mm valves mere implanted in the mitral position of five sheep. In a clinical trial, 306 patients with isolated mitral or aortic valve replacements were followed up for a total of 371 patient years (mean 1.37 years and range 0-4 years). RESULTS: The hydrodynamic performance was comparable to that of proven clinical models. The accelerated testing indicated lifetimes in excess of 50 years and the animal trials showed the valve to be safe. In the clinical trial, there was no incidence of structural failure or paravalvular leak. The linearized rate of late thromboembolism was 6.2%/patient-year (pty), anticoagulant related hemorrhage 0.54%/pty and infective endocarditis 0.54%/pty. At two years, the total actuarial survival was 89.5%. The higher incidence of thromboembolism and the very low incidence of anticoagulant related hemorrhage illustrate the difficulty in the management of anticoagulant therapy in a developing country, while the low incidence of endocarditis reflects their greater resistance to infection. CONCLUSION: These data clearly showed the valve to be safe and comparable to other similar valves in clinical use.

Structural studies on bovine bioprosthetic tissues and their in vivo calcification: prevention via drug delivery.

Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common end-stage phenomenon affecting a wide variety of bioprostheses. To study the process of calcification in tissue prosthetics, glutaraldehyde-treated bovine pericardium, dura mater and fascialata were implanted subcutaneously in rats and retrieved 21 days later and thereby morphological findings were correlated with biochemically determined levels of calcium. Transmission electron microscopy showed that calcification primarily involved the surface of collagen fibrils and the interfibrillar spaces. The deposition of calcium was higher with dura and fascia prostheses compared to pericardium. However, the release of Fe3+ ions from chitosan matrix had substantially inhibited the deposits of calcium in all implanted tissues. It seems that the structural and anatomical features of the tissue is one of the important factors for tissue-associated calcification. It is also confirmed that glutaraldehyde-preserved pericardium is the most suitable material for the development of cardiac prosthesis, with an appropriate drug combination therapy for prevention of pathological calcification.

Levels of cerium in the tissues of rats fed a magnesium-restricted and cerium-adulterated diet.

Cerium, a lanthanide, is the most abundant rare earth element present in monazite and is biologically active. It has been postulated that cerium toxicity in conjunction with magnesium deficiency causes tropical endomyocardial fibrosis, a restrictive human cardiomyopathy (Valiathan et al. 1989; Valiathan and Kartha 1990). Generally, lanthanides are known to be poorly absorbed (Durbin et al. 1956; Evans 1990). The present study was carried out to ascertain whether magnesium deficiency promotes accumulation of cerium in various organs of rats.

Prevention of calcification of tissue valves.

In this study an attempt was made to find an optimum method of chemical treatment to prevent the calcification of bioprosthetic heart valves. Bovine pericardium was washed in a 5% sodium chloride solution followed by trypsin (Tr) treatment and was kept in 0.1% glutaraldehyde (GA) with a gradual increase in concentration up to 0.25% GA and finally posttreated with a 4% chitosan (Ch) solution. Fresh, 0.2% GA, 0.625% GA, and sodium chloride-Tr-GA treated pericardial samples were taken for comparative study. Tensile testing showed comparable strength and elongation at the breaking point for all groups. The thermal shrinkage studies indicated merit of the proposed treatment (5% sodium chloride-trypsin-glutaraldehyde treated pericardia with chitosan and without chitosan posttreatment). Collagenase assay showed that all differently treated (GA) materials were equally resistant to collagenase. All samples were implanted subcutaneously in rats for 2, 4, 8, or 12 weeks for calcification study. Morphological and mineral analyses showed complete prevention of calcification in sodium chloride-trypsin-GA-chitosan treated pericardium (Ca was 1.1 +/- 0.27 mg/g, von Kossa 0) at the 12th week of implantation.